The necessity and functional significance of neurotransmitter co-transmission remains unclear. The glutamatergic 'KNDy' neurons co-express kisspeptin, neurokinin B (NKB) and dynorphin and exhibit a highly stereotyped synchronized behavior that reads out to the gonadotropin-releasing hormone (GnRH) neuron dendrons to drive episodic hormone secretion. Using expansion microscopy, we show that KNDy neurons make abundant close, non-synaptic appositions with the GnRH neuron dendron. Electrophysiology and confocal GCaMP6 imaging demonstrated that, despite all three neuropeptides being released from KNDy terminals, only kisspeptin was able to activate the GnRH neuron dendron. Mice with a selective deletion of kisspeptin from KNDy neurons failed to exhibit pulsatile hormone secretion but maintained synchronized episodic KNDy neuron behavior thought to depend on recurrent NKB and dynorphin transmission. This indicates that KNDy neurons drive episodic hormone secretion through highly redundant neuropeptide co-transmission orchestrated by differential postsynaptic neuropeptide receptor expression at the GnRH neuron dendron and KNDy neuron.

中文翻译：

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GnRH神经元树突偶发激活的高度冗余神经肽体积共传递

神经递质共传递的必要性和功能意义仍不清楚。谷氨酸能“KNDy”神经元共同表达 Kisspeptin、神经激肽 B (NKB) 和强啡肽，并表现出高度刻板的同步行为，该行为会读出促性腺激素释放激素 (GnRH) 神经元树突以驱动间歇性激素分泌。使用扩展显微镜，我们显示 KNDy 神经元与 GnRH 神经元树突产生大量紧密的非突触并置。电生理学和共聚焦 GCaMP6 成像表明，尽管所有三种神经肽都从 KNDy 末端释放，但只有 Kisspeptin 能够激活 GnRH 神经元树突。从 KNDy 神经元中选择性删除 Kisspeptin 的小鼠未能表现出搏动性激素分泌，但保持同步的发作性 KNDy 神经元行为，这被认为取决于复发性 NKB 和强啡肽的传递。这表明 KNDy 神经元通过 GnRH 神经元树突和 KNDy 神经元的不同突触后神经肽受体表达协调的高度冗余的神经肽共传递来驱动发作性激素分泌。